2-[2-(4-Dibenzo[b,f]-[1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol (quetiapine) and its salts were disclosed in Eur. Pat. No. 0240228 and they are useful for their antidopaminergic activity, for example, as an antipsychotic or neuroleptic.
Various processes for preparation of quetiapine and 2-[2-(4-Dibenzo[b,f]-[1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol hemifumarate (quetiapine fumarate) were described in EP 0240 228, EP 0282236, WO 01/55125 and WO 99/06381. According to the teachings of literature, quetiapine fumarate was crystallized from ethanolic solution containing quetiapine free base and fumaric acid. Quetiapine fumarate prepared according this method fails to produce well defined reproducible crystalline form.
It has now been discovered stable, reproducible two crystalline forms of quetiapine fumarate. It has also been discovered that the crystalline forms of quetiapine fumarate can be obtained in very pure state. Thus, they can be used as active ingredients in pharmaceutical preparations.
Thus, the object of the present invention is to provide quetiapine fumarate in stable and reproducible crystalline forms, processes for their preparation and pharmaceutical composition containing them.
The present invention also provides amorphous form of quetiapine with adequate stability and good dissolution properties.
Thus another object of the present invention is to provide amorphous form of quetiapine fumarate, a process for preparing it and a pharmaceutical composition containing it.